Health & Disease - NYAS

Overview

First identified nearly a century ago for its essential role in maintaining bone health, vitamin D has recently undergone a renaissance of interest due to the resurgence of vitamin D deficiency and the identification of vitamin D receptors in tissues and cells outside the skeletal system. Indeed, a growing body of evidence indicates that vitamin D has several extraskeletal functions and plays a key role in the immune, cardiovascular, and nervous systems. Furthermore, a growing body of research links vitamin D status to health and vitamin D deficiency to the risk of developing certain diseases, including cancers, multiple sclerosis, type 1 diabetes, rheumatoid arthritis, hypertension, and cardiovascular disease. On September 21, 2012, basic science and clinical researchers gathered to discuss non-classical effects at the Vitamin D: Beyond Bone conference presented by the Abbott Nutrition Health Institute and The New York Academy of Sciences.

Speakers

Daniel D. Bikle, MD, PhD
University of California, San Francisco and VA Medical Center

Ricardo Boland, PhD
Universidad Nacional del Sur, Argentina

Sylvia Christakos, PhD
UMDNJ–New Jersey Medical School

Luigi Ferrucci, MD, PhD
National Institute on Aging

David G. Gardner, MD
University of California, San Francisco

Martin Hewison, PhD
University of California, Los Angeles

Lily Li
Mount Sinai School of Medicine

Anastassios G. Pittas, MD
Tufts Medical Center

Erica Rutten, PhD
Ciro +, Centre of Expertise for Chronic Organ Failure

Igor N. Sergeev, PhD, DSc
South Dakota State University

Carol L. Wagner, MD
Medical University of South Carolina

Introduction

Keynote Speaker

Daniel D. Bikle
University of California, San Francisco and VA Medical Center

Highlights

Two major forms of vitamin D are important for human health: vitamin D₃, which is synthesized in sun-exposed skin, and vitamin D₂, which is synthesized in certain plants.
Vitamin D is obtained through diet and sun exposure in the form of inactive precursors. The biologically active form of vitamin D, 1,25-dihydroxyvitamin D, is produced via a two-step enzymatic process, predominantly in the liver and kidneys.
The classical function of vitamin D is to maintain the integrity of the skeleton by modulating calcium homeostasis, but recent studies have uncovered several extraskeletal functions.
The current recommended dietary reference values for vitamin D may be inadequate, especially for those at risk for vitamin D deficiency.

Synthesis and metabolism of vitamin D

Vitamin D was first identified early in the 20th century as an essential nutrient. It is now recognized to comprise a group of fat-soluble prohormones, substances that are precursors to hormones but have minimal hormonal activity. Two major forms of vitamin D are important to human health—vitamin D₂ (ergocalciferol) and vitamin D₃ (cholecalciferol)—which differ chemically only in the structures of their side chains. Vitamin D₃ is produced in the skin through the action of sunlight (in particular, UVB radiation) on 7-dehydrocholesterol; analogously, vitamin D₂ is synthesized in some plants and fungi via photoconversion of ergosterol.

Although sunlight exposure is our main source of vitamin D, it can also be obtained through diet or dietary supplements. Very few foods, however, naturally contain meaningful amounts of vitamin D. Good sources include cod liver oil, salmon, tuna, and other fatty fish, as well as fortified foods, such as milk, yogurt, and orange juice.

Vitamin D metabolism. (Image courtesy of Sylvia Christakos)

Vitamin D obtained through diet, supplements, or sun exposure is biologically inactive and must undergo metabolism to become active. Vitamin D₂ and D₃ are transported in the blood by vitamin D-binding protein to the liver and enzymatically hydroxylated at carbon 25 to form 25-hydroxyvitamin D (25(OH)D). Although 25(OH)D is still biologically inert, it represents the major circulating form that is measured to assess vitamin D status. The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)₂D), is produced predominantly in the kidney but can also form in a variety of other tissues, including the skin and bone, and in immune cells. Compared with 25(OH)D, 1,25(OH)₂D is generally not a reliable indicator of vitamin D status because it has a shorter half-life and its serum level changes in response to calcium, phosphate, and parathyroid hormone (PTH).

Vitamin D mechanism of action

The classical function of the active form of vitamin D is to maintain the integrity of the skeleton by regulating calcium and phosphorus homeostasis. In response to low blood calcium levels, the parathyroid gland secretes PTH, which induces expression of CYP27B1, the enzyme that catalyzes formation of 1,25(OH)₂D. This active form binds to the vitamin D receptor (VDR)—which regulates gene expression by binding predominantly to vitamin D-responsive elements in the promoter regions of target genes—stimulating intestinal absorption of calcium and phosphate, the release of calcium from bone, and calcium re-absorption in the kidney.

Keynote address: Vitamin D dietary reference intakes

In 2010 the Institute of Medicine (IOM) evaluated health outcomes associated with vitamin D and calcium and proposed updated Dietary Reference Intake (DRI) values reflecting new data on optimal levels of these minerals. The IOM recommended a 25(OH)D serum level of at least 20 ng/mL (50 nM) but considered levels up to 50 ng/mL (125 nM) safe. A 600 IU daily intake of vitamin D is deemed adequate for most people but up to 4000 IU is considered safe. The IOM concluded that 97.5% of the U.S. population have 25(OH)D levels greater than 20 ng/mL and therefore do not need vitamin D supplementation.

Daniel Bikle from the University of California, San Francisco and VA Medical Center gave his perspective on these recommendations in his keynote address. He pointed out that the recommendations are for the general population, not patients, and are based only on studies of vitamin D’s classical effects on bone. Moreover, the IOM based its conclusion that nearly everyone in the U.S. population is vitamin D sufficient on data from National Health and Nutrition Examination Surveys (NHANES), which were weighted toward healthy Caucasians and excluded the population living in the northern part of the country in the winter. Bikle surveyed additional studies that question the adequacy of the vitamin D status in many populations, concluding, “I question the IOM conclusion that 97.5% of the population in the U.S. maintain 25(OH)D levels above 20 ng/ml.”

Bikle also questioned whether the IOM recommendations meet the needs of the elderly, a population that is particularly vulnerable to vitamin D deficiency due to age-related decreases in cutaneous vitamin D production, dietary intake, intestinal absorption, 1,25(OH)₂D production, and intestinal response to 1,25(OH)₂D. He surveyed data on the relationship between vitamin D status and bone density, mobility, fall rates, and fracture risk and concluded that, “50 nM or 20 ng/ml [may not be optimal] for the elderly individual who’s at the greatest risk of vitamin D deficiency on the one hand and of fractures on the other.”

Bikle recommended that particular subsets of the population be tested for vitamin D deficiency, including women and men over age 65 and 70, respectively; those who are institutionalized; those with dark complexions living in temperate latitudes; those who avoid the sun or dairy products; those with osteoporotic fractures; those with malabsorption; those undergoing bariatric surgery; those with chronic kidney disease; and those taking certain drugs that alter metabolism.

In recent decades researchers have uncovered several non-classical extraskeletal functions of vitamin D. The Vitamin D: Beyond Bone conference explored these, presenting vitamin D’s multifunctional role in immunity, cardiovascular health, cancer, pregnancy, infection, diabetes, cognitive function, and muscle function; its molecular mechanisms of action; and recent changes to nutritional guidelines. The conference encouraged cross-disciplinary dialogue, identified research gaps, and helped to build communities, develop partnerships, and translate basic research findings and epidemiological data into strategies that may promote public health.

Video Chapters
00:01 1. Introduction; The IOM recommendations
16:23 2. Vitamin D deficieny in the elderly
22:07 3. Recommendation adequacy
30:00 4. Who should be tested?
38:58 5. Therapeutic considerations
43:00 6. Summary and conclusions

Non-classical Roles of Vitamin D, Part 1

Speakers

Sylvia Christakos
University of Medicine and Dentistry New Jersey (UMDNJ)–New Jersey Medical School

Martin Hewison
University of California, Los Angeles

David G. Gardner
University of California, San Francisco

Carol L. Wagner
Medical University of South Carolina

Highlights

Vitamin D inhibits the growth of breast cancer cells in vitro.
Vitamin D reverses paralysis in a mouse model of multiple sclerosis.
Vitamin D modulates, directly or indirectly, the function of several immune system cells.
Vitamin D may exert a protective effect on the cardiovascular system.
Supplementation with 4000 IU of vitamin D per day appears to be safe and effective for pregnant women.

Vitamin D’s impacts on cancer and multiple sclerosis

In addition to its principal role in the regulation of calcium homeostasis, recent in vitro and animal studies suggest that vitamin D inhibits the growth of breast, colon, and prostate cancer cells and may provide protection against certain immune-mediated disorders, such as type 1 diabetes and multiple sclerosis (MS). Sylvia Christakos from UMDNJ opened the meeting by discussing her research into the molecular mechanisms that underlie its impact on breast cancer and the immune system. Her studies have revealed that 1,25(OH)₂D₃ inhibits the growth of breast cancer cells in culture, in part by inducing the transcription factor and potential tumor suppressor protein C/EBPα (providing evidence that C/EBPα may be a candidate target for breast cancer treatment).

Christakos also described research demonstrating that vitamin D suppresses the development of experimental allergic encephalitis (EAE), the mouse model of MS. She investigated vitamin D’s effects on a class of helper T cells that produce the inflammatory cytokine IL-17, which has been reported to play a critical role in mediating inflammatory responses and autoimmune diseases, including MS. 1,25(OH)₂D₃ inhibited the transcription of IL-17 in human CD4⁺ T cells in vitro and, in in vivo studies in EAE mice, down-regulated IL-17 levels in CD4⁺ T cells and reversed the onset of paralysis. These findings suggest that inhibition of IL-17 transcription may be one mechanism by which 1,25(OH)₂D₃ exerts its immunosuppressive effects. “Many of the same genes are present in humans and mice, and they act similarly, so minimally the findings … may suggest mechanisms involving similar pathways in humans that could lead to the identification of new therapies,” Christakos concluded.

Video Chapters
00:01 1. Introduction and overview
04:12 2. Vitamin D’s impact beyond the skeletal system
11:24 3. Vitamin D and breast cancer
18:11 4. Vitamin D and multiple sclerosis
25:32 5. Summary, acknowledgements, and conclusions

Vitamin D in immune function and disease prevention

Martin Hewison from the University of California, Los Angeles expanded the discussion of vitamin D’s potent immunomodulatory effects, focusing on cellular machinery that mediates the activities of the adaptive and innate immune systems. Nearly all immune system cells express the vitamin D receptor (VDR); cells of the innate immune system, including macrophages and dendritic cells, also express the enzyme CYP27B1, and thus can activate 25(OH)D locally. Hewison’s research has shown that locally-activated vitamin D in macrophages can trigger the up-regulation of antibacterial proteins, such as LL37 (also known as cathelicidin), and can enhance the killing of bacterial pathogens. Ex vivo studies of human innate immune cells revealed that LL37 expression levels vary with vitamin D status, suggesting that vitamin D deficiency may potentially impair the LL37-mediated response to infection. Cytokines produced by other immune system cells enhance or suppress this vitamin D-mediated immune response by modulating vitamin D metabolism within innate immune cells.

Hewison’s group also discovered a similar intracrine vitamin D system in dendritic cells (DCs)—innate immune cells that primarily deliver bacterial antigen to cells of the adaptive immune system. In this case, locally-activated vitamin D inhibits DC maturation, thereby suppressing antigen presentation and indirectly modulating helper T-cell function. Hewison noted that the active vitamin D produced by DCs, as well as by macrophages, can also act in a paracrine fashion to directly regulate the function of all the various T-cell types by modulating the expression of key T-cell genes. Thus, vitamin D appears to promote immune tolerance and to suppress inflammation and autoimmunity.

Vitamin D affects the activity of macrophages and DCs to modulate adaptive and innate immunity. (Image courtesy of Martin Hewison)

Investigating the link between vitamin D status and autoimmune diseases, such as inflammatory bowel disease (IBD), Hewison’s lab found that inducing short-term vitamin D-deficiency in mice increased the severity of experimentally-induced IBD. Vitamin D-deficient mice exhibited decreased expression of an antibacterial protein in the gastrointestinal tract and increased levels of bacteria in the colon, suggesting an additional antibacterial function for vitamin D and a potential interaction between IBD and the microbiota.

Hewison ended his talk with a look at vitamin D’s immunomodulatory function during pregnancy. Pregnant women tend to be vitamin D deficient. Hewison’s research has uncovered antibacterial and anti-inflammatory actions of vitamin D in placental trophoblast cells, suggesting that vitamin D deficiency may have implications for fetal development, preterm birth, fetal programming of adult disease, and maternal blood pressure. Hewison concluded by suggesting that vitamin D deficiency might impact a wide range of immune-related disorders.

Video Chapters
00:01 1. Introduction
03:00 2. Vitamin D and bacterial killing; Tuberculosis and other disease studies
12:55 3. CYP27B1/VDR interactions; Inflammatory bowel disease and the microbiota
20:18 4. Vitamin D and pregnancy
26:12 5. Summary, acknowledgements, and conclusions

Vitamin D during pregnancy and lactation

Carol L. Wagner from the Medical University of South Carolina continued the theme of vitamin D action during pregnancy and lactation, focusing on the results of her recent vitamin D supplementation trials in pregnant women. Wagner and colleagues have found striking evidence of global vitamin D deficiency during pregnancy, particularly among darker pigmented individuals. Epidemiological studies have revealed that vitamin D deficiency is linked with a higher risk of maternal preeclampsia, an increased risk of gingivitis and periodontal disease in the mother, impaired fetal growth, impaired childhood dentition, and an increased risk of infection by respiratory syncytial virus (RSV).

To determine the most effective safe dose of vitamin D for pregnant women, Wagner and colleagues conducted studies with two different populations of pregnant women, each split into groups receiving 400IU, 2000IU, or 4000 IU of vitamin D₃ per day until delivery. The studies found that 4000 IU/day is needed to achieve vitamin D sufficiency (the IOM currently recommends a daily dose of 600 IU/day for the general population). Perhaps more surprisingly, 25(OH)D levels had a direct and positive influence on 1,25(OH)₂D levels throughout pregnancy, which has not been observed at any other time in life. No adverse events were attributed to supplementation; in fact, Wagner noted a trend towards lower rates of pregnancy complications in the 2000 IU and 4000 IU groups, compared with the 400 IU group, and towards lower rates of comorbidities during pregnancy with increasing 25(OH)D levels. She concluded that 4000 IU/day is safe and achieves vitamin D sufficiency in pregnant women.

Wagner is now investigating how vitamin D status affects immune function in the mother and her developing fetus and whether maternal D supplementation meets the requirements of both the mother and her nursing infant.

Video Chapters
00:01 1. Introduction; Earlier studies
05:50 2. Epidemiological data; The NICHD supplementation study
11:23 3. The Thrasher Study; Combined study datasets
18:25 4. The Kellogg Project; Supplementation and mother’s milk
23:23 5. Summary and conclusions

Vitamin D and the cardiovascular system

Recent studies suggest that vitamin D may have a protective effect on the cardiovascular system: vitamin D deficiency is associated with high blood pressure and heart enlargement in rats; patients with congestive heart failure have reduced levels of circulating vitamin D; and vitamin D and VDR activation inhibits heart enlargement in rodents. David Gardner from the University of California, San Francisco investigated the molecular mechanisms underlying vitamin D’s cardiovascular effects using mouse models with VDR selectively deleted in either cardiac myocytes or endothelial cells.

Deletion of VDR in myocytes resulted in myocyte enlargement and in expression of genes involved in hypertrophy. Deletion of VDR in mice genetically engineered to accumulate excess fat in myocytes—a condition known as cardiac steatosis that is associated with obesity and diabetes in humans—amplified the pathological effects of cardiac steatosis, suggesting that VDR deletion, and possibly vitamin D deficiency, may sensitize the heart to pathological stimuli. VDR deletion in endothelial cells in vitro impaired the vasorelaxation that normally occurs in response to acetylcholine neurotransmitter. Furthermore, VDR deletion in endothelial cells in vivo resulted in a greater increase in blood pressure in response to the vasoconstricting hormone angiotensin. Taken together, Gardner’s findings suggest that vitamin D and vitamin D analogues may be useful in the management of heart disorders that involve cardiac hypertrophy.

Video Chapters
00:01 1. Introduction
03:21 2. VDR activators and hypertrophy; Liganded VDR and the cardiac myocyte
12:25 3. VDR deficiency and cardiomyophathic stimuli
20:28 4. VDR deletion in murine endothelial cells
25:37 5. Summary, acknowledgements, and conclusions

Non-classical Roles of Vitamin D, Part 2

Speakers

Igor N. Sergeev, South Dakota State University

Erica Rutten, Ciro +, Centre of Expertise for Chronic Organ Failure

Lily Li, Mount Sinai School of Medicine

Highlights

Vitamin D induces apoptosis in fat cells, suggesting that it may one day be useful in the treatment and prevention of obesity.
Vitamin D may help to preserve lung function in patients with chronic obstructive pulmonary disorder.
Vitamin D reduces the erythropoietin requirements of hemodialysis patients with end-stage renal disease.

Vitamin D and apoptosis in obesity

The discussion of the non-classical roles of vitamin D continued with a series of short talks by early career investigators. Epidemiological studies have associated low vitamin D status with an increased risk of obesity. Igor N. Sergeev from South Dakota State University has found that 1,25(OH)₂D₃ triggers programmed cell death in fat cells by inducing a sustained increase in calcium and by activating calcium-dependent proteases. He noted that inducing apoptosis in fat cells is emerging as a potential strategy for treating and preventing obesity. Using a mouse model of diet-induced obesity, Sergeev showed that supplementation with calcium and vitamin D reduced body fat and weight gain and improved biomarkers of adiposity. Sergeev suggested that vitamin D and calcium might prove useful in the treatment and prevention of obesity.

Vitamin D and calcium supplementation decrease body weight gain in diet-induced obese mice. (Image courtesy of Igor Sergeev)

Vitamin D and lung function

Recent studies have found that vitamin D deficiency is prevalent among people with chronic obstructive pulmonary disease (COPD), an irreversible lung condition that includes chronic bronchitis and emphysema and is primarily caused by smoking. The prevalence of vitamin D deficiency increases with the severity of COPD. Erica Rutten from the Ciro +, Centre of Expertise for Chronic Organ Failure conducted a cross-sectional study of patients with moderate to very severe COPD: 58% were vitamin D deficient. She observed that lung function was positively associated with plasma vitamin D levels, even after correcting for age, gender, and body mass index, and concluded that vitamin D may play a role in lung pathology in patients with COPD.

Vitamin D deficiency may play a role in lung pathology in chronic obstructive pulmonary disease (COPD). (Image courtesy of Erica Rutten)

Vitamin D and chronic kidney disease

Vitamin D deficiency is also common in hemodialysis patients with end-stage renal disease. Lily Li and colleagues from Mount Sinai School of Medicine are conducting an ongoing randomized controlled trial to determine whether correcting vitamin D deficiency decreases vitamin D-deficient hemodialysis patients’ requirements for erythropoietin, a hormone produced by the kidneys that is essential for red blood cell production. The group hypothesized that vitamin D deficiency causes dysregulation of innate immunity, leading to inflammation and altered iron metabolism and contributing to erythropoietin resistance. To date, vitamin D supplementation for 3 or 6 months has safely and effectively increased patients’ 25(OH)D levels and has reduced their requirements for erythropoietin. Ongoing studies aim to determine the immunologic effects of vitamin D repletion in these patients.

Policy and Clinical Applications

Speakers

Anastassios G. Pittas
Tufts Medical Center

Ricardo Boland
Universidad Nacional del Sur, Argentina

Luigi Ferrucci
National Institute on Aging

Highlights

Low vitamin D status is associated with type 2 diabetes, but it remains unclear whether there is a causal relationship between vitamin D and diabetes.
Vitamin D regulates skeletal muscle cell proliferation and function via classical and non-classical molecular mechanisms.
Vitamin D status is associated with several aspects of physical and cognitive function in the elderly.

Vitamin D and type 2 diabetes

Vitamin D supplementation has emerged as a potential strategy for the prevention and management of type 2 diabetes. In his talk, Anastassios Pittas from Tufts Medical Center evaluated whether the available evidence supports a scientifically valid causal association between vitamin D and type 2 diabetes. Using observational data from the Nurses Health Study, Pittas has investigated the association between vitamin D and calcium intake and the development of type 2 diabetes. He found that women who reported the highest levels of calcium and vitamin D intake had a 33% lower risk of developing diabetes compared to those with the lowest intakes of both nutrients. He also observed an inverse relationship between plasma 25(OH)D concentration and risk of incident type 2 diabetes, such that women with higher levels of 25(OH)D had a lower risk of developing diabetes. Moreover, after repeatedly assessing vitamin D status over time in patients at risk for diabetes, he found that progression from pre-diabetes to diabetes declined with increasing concentrations of 25(OH)D.

These and other data suggest that vitamin D is associated with diabetes, but before accepting that a causal relationship exists, “we need to consider alternative explanations,” says Pittas. Because dietary intake of vitamin D and cutaneous synthesis of vitamin D are associated with healthy diets and behaviors, it is difficult to distinguish these potentially confounding factors from the effect of vitamin D itself, says Pittas. Furthermore, vitamin D status is associated with a variety of other factors, many of which are independently associated with diabetes, including physical inactivity, obesity, and dietary patterns. “So, is vitamin D simply a marker of increased risk for type 2 diabetes?” Pittas asked. “In other words, the strong association that we see with type 2 diabetes does not necessarily mean that supplementation would be beneficial.” Therefore, he says, randomized clinical trials are needed to test the hypothesis that vitamin D can modify diabetes risk.

Pittas’s randomized controlled trial—aimed to determine whether vitamin D supplementation would improve glucose homeostasis in patients at high risk for diabetes—showed that short-term vitamin D supplementation improved beta-cell function and attenuated the rise in glycated hemoglobin, a biomarker for diabetes. “In my mind, [vitamin D supplementation] for type 2 diabetes is a promising idea, but is yet unproven,” Pittas concluded.

Video Chapters
00:01 1. Introduction
03:14 2. Biological plausibility; Specificity
05:58 3. Temporal relationship, association strength, dose response, and coherence
11:00 4. Experimental evidence and alternative explanations; Studies
19:40 5. Vitamin D, diabetes, and ethnicity
23:38 6. Summary and conclusions

Vitamin D and muscle function

Multiple lines of evidence suggest that vitamin D plays a role in muscle function: muscle weakness and atrophy are common symptoms of vitamin D deficiency; 1,25(OH)₂D₃ stimulates muscle synthesis in vitamin D-deficient rats; and cellular studies have revealed the presence of the VDR in skeletal muscle. Ricardo Boland from Universidad Nacional del Sur, Argentina reviewed the molecular mechanisms by which 1,25(OH)₂D₃ regulates skeletal muscle cell proliferation and differentiation. In skeletal muscle cells, vitamin D can function via a classical genomic mechanism, triggering VDR-mediated changes in the expression of genes involved in muscle cell proliferation and differentiation.

Boland has discovered that vitamin D can also function in skeletal muscle cells via a non-classical mechanism involving the activation of transmembrane second messenger systems, calcium influx, and the growth-regulating signaling pathway known as the mitogen-activated protein kinase (MAPK) cascade. 1,25(OH)₂D₃ stimulates the translocation of VDR from the nucleus to the membrane, where it complexes with a calcium channel protein. At the cell membrane, VDR also forms a complex with the protein Src, which signals upstream of the MAPK cascade. These molecular mechanisms help to clarify how vitamin D regulates skeletal muscle cell growth and contractility and may aid the development of treatments for skeletal muscle disorders.

An overview of the genomic and non-genomic modes of action of 1,25OH₂D₃ in skeletal muscle cells. (Image courtesy of Ricardo Boland)

Video Chapters
00:01 1. Introduction and background
05:45 2. Calcium influx; Capacitative calcium entry; SOC, TRP, and VDR
13:30 3. INAD-scaffold protein; Src tyrosine kinase; The ERK1/2 pathway
26:20 4. Akt activation; 1,25-dependent Src activation
33:12 5. Summary and conclusions

Vitamin D and Physical and Cognitive Function in Older Persons

Luigi Ferrucci from the National Institute on Aging reviewed the connections between vitamin D and aging. He and others have demonstrated that low 25(OH)D status is associated with mobility limitation and disability in older adults. He explored the basic pathways that may mediate these effects on physical and cognitive function in older persons, focusing on four major aging phenotypes that are related to the biological functions of vitamin D: changes in body composition, imbalances in energy production and utilization, homeostatic dysregulation, and neurodegeneration.

Ferrucci addressed changes in body composition first, showing that low serum levels of 25(OH)D are associated with a higher incidence of obesity and a higher probability of developing obesity, although the mechanisms remain unclear. In muscle tissue, expression of the VDR declines with age, and epidemiological studies have linked low vitamin D levels with loss of muscle strength and mass. These studies reveal some of the ways in which vitamin D may influence body composition.

Next, Ferrucci addressed energy homeostasis. High vitamin D levels are strongly correlated with higher levels of aerobic fitness and peak aerobic capacity, suggesting that low vitamin D levels may give rise to imbalances in energy production and utilization. Furthermore, VDR appears to localize in mitochondria in human blood cells, suggesting that vitamin D may influence energy homeostasis by regulating mitochondrial function.

In terms of homeostatic dysregulation, Ferrucci focused on vitamin D’s anti-cancer and anti-inflammatory actions. At the molecular level, 1,25(OH)₂D₃ may reduce inflammation by blocking the synthesis and action of prostaglandins and pro-inflammatory cytokines. A systematic review of 219 cross-sectional studies in the literature—designed to evaluate whether vitamin D levels are associated with the risk for autoimmune diseases and whether vitamin D supplementation can modify the course of the diseases—revealed that supplementation with vitamin D may reduce the risk of autoimmune disease. However, randomized controlled trials are needed to establish the clinical efficacy of vitamin D supplementation.

Finally, in terms of neurodegeneration, Ferrucci showed that low levels of vitamin D are associated with an accelerated decline in cognitive function, while higher levels of vitamin D intake are associated with a lower risk of Alzheimer’s disease. Ferrucci has also identified an association between low serum levels of 25(OH)D and symptoms of depression in older men and women.

Ferrucci ended by calling for randomized, controlled intervention studies of vitamin D to determine whether it can slow the development of physical and cognitive disability.

Video Chapters
00:01 1. Introduction
06:02 2. Pathways to cognitive and physical frailty; Changes in body composition
16:24 3. Energy imbalance; Homeostatic dysregulation
20:15 4. Neurodegeneration; Going forward; Conclusions

Panel Discussion

Moderator

Mandana Arabi
The Sackler Institute for Nutrition Science

Video Chapters
00:01 1. Does one size fit all?
09:22 2. Sun avoidance; Categorization; Interpreting study data
21:24 3. Prescribing dosage; Fortified foods; Vitamin D2 vs. D3
35:30 4. Vitamin K2; Serum 25-hydroxyvitamin

Open Questions

How do the extraskeletal biological responses observed in vitro and in animal models relate to human disease?
Does the adjustment of vitamin D status correct vitamin D-mediated immune dysfunction?
Does vitamin D status affect the composition of the gut microbiota?
What are the circulating biomarkers of vitamin D-related immune function?
What vitamin D supplementation level should be recommended for pregnant and lactating women?
Is vitamin D supplementation beneficial to vitamin D-deficient patients with chronic obstructive pulmonary disease?
Does vitamin D modify the risk of diabetes?
Can vitamin D supplementation slow down the development of physical and cognitive disability in the elderly?
When measuring vitamin D status, is it more meaningful to measure total 25(OH)D levels or only the fraction of 25(OH)D that is not bound to protein?
Does vitamin D supplementation provide any clinical benefit other than its well-documented effects on bone?

Speakers

Organizers

Heike Bischoff-Ferrari, MD, MPH

University of Zurich, Switzerland
website | publications

Heike Bischoff-Ferrari is an MD and clinical researcher with specialty board certifications in general medicine, geriatrics, and physical medicine and rehabilitation at the University of Zurich, Switzerland. After her clinical training at the University of Basel, she was a fellow at the Department of Rheumatology, Immunology, and Allergy at the Brigham and Women’s Hospital in Boston and was appointed to the faculty at Harvard Medical School. Bischoff-Ferrari holds an MPH from Harvard School of Public Health and a Doctor of Public Health from the Department of Nutrition at Harvard School of Public Health. Bischoff-Ferrari has an ongoing appointment as a visiting scientist at the Human Research Center on Nutrition and Aging at Tufts University. She holds a primary faculty appointment at the Department of Rheumatology at the University Hospital in Zurich, Switzerland and received a Swiss National Foundations professorship in 2007. In 2008, she became the director of the Center on Aging and Mobility at the University of Zurich. Bischoff-Ferrari’s research focus is improving musculoskeletal health among the senior population with a focus on falls, fractures, and osteoarthritis. One particular interest is to define the role of vitamin D in the context of aging and musculoskeletal health.

Martin Hewison, PhD

University of California, Los Angeles
e-mail | website | publications

Martin Hewison is currently a professor in residence at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA), where his group has an established interest in the role of vitamin D in human physiology, and in particular the interaction between vitamin D and the immune system. Hewison gained his PhD in biochemistry from Guy’s Hospital Medical School, London and spent nine years at University College London. After moving to the University of Birmingham he established the UK’s major vitamin D research group, leading to an appointment as a professor in molecular endocrinology in 2004. In 2005 he joined Cedars-Sinai Medical Center, Los Angeles and moved to neighboring UCLA at the end of 2007. Hewison has published over 160 peer-reviewed manuscripts focused on various facets of steroid hormone endocrinology.

Nabeeha Mujeeb Kazi, MIA, MPH

Humanitas Global Development
e-mail | website

Nabeeha Mujeeb Kazi is managing director of Humanitas Global Development (HGD). She has directed high-profile global food-security initiatives and designed advocacy, public–private partnership, community mobilization, behavior change, and stakeholder engagement programs. Kazi’s team has collaborated with numerous high-profile international organizations including Global Alliance for Improved Nutrition, World Bank, World Health Organization, Save the Children, and UNICEF, among others. Kazi served as Senior Vice President and Partner at Fleishman-Hillard, a global communications firm, and has worked for the Clinton Foundation’s HIV/AIDS Initiative, focusing on Caribbean and African countries, and for the International Maize and Wheat Improvement Center (CIMMYT) in Mexico. Kazi serves on the boards of FINCA International and United Neighborhood Centers of America and has served on several taskforces and committees with partners like Scaling Up Nutrition, Millennium Villages, Feed the Future, and the New York Academy of Sciences. Kazi has dual Master’s degrees in public health and international affairs from Columbia University.

Hawley K. Linke, PhD

Abbott Nutrition
e-mail | website | publications

Hawley K. Linke is a senior scientist in the Global Discovery Group at Abbott Nutrition. Her early expertise arose from postdoctoral studies in mitochondrial gene identification at Stanford University Medical School and from her study of human viral gene expression for her PhD from UCLA’s Molecular Biology Institute. She joined Abbott Laboratories Diagnostics Division, Hepatitis-AIDS investigation group, before transferring to Abbott Nutrition. Her contributions to nutrition research include the development and exploitation of industrial-scale expression technologies producing genetically modified and unmodified human proteins for nutritional applications and clinical studies demonstrating therapeutic innovations in infant formula. As an expert in vitamin D, she advises the division on nutritional products to optimize its pleiotropic health benefits. She focuses on technologies for women’s health, neurogastroenterology, and manipulation of the microbiome.

Rosemary E. Riley, PhD, LD

Abbott Nutrition Health Institute
e-mail | website | publications

Rosemary E. Riley is senior manager for science programs at the Abbott Nutrition Health Institute, where she is responsible for developing and directing programs that educate health care professionals throughout the world on the importance of nutrition as therapy to improve patient outcomes. While at Abbott, Riley has worked on a variety of nutrition initiatives, including a comprehensive, multidisciplinary medically supervised weight management program, geriatric nutrition, sports nutrition, women’s health—with a focus on bone health—and diabetes. She also has experience in strategic discovery and evaluation of ingredients and technology to address these conditions.

Carol L. Wagner, MD

Medical University of South Carolina
e-mail | website | publications

As an academic neonatologist for more than 20 years, Carol L. Wagner has been involved in basic science, translational, and clinical studies. She holds an MD from Boston School of Medicine. She completed both her pediatric residency and neonatalñperinatal fellowship at the University of Rochester. She is a professor of pediatrics and the associate director of the Clinical and Translational Research Center at the Medical University of South Carolina. Wagner’s current research interests are vitamin D requirements during pregnancy and lactation and human milk bioactivity and its effect on gut maturation.

Mandana Arabi, MD, PhD

The Sackler Institute for Nutrition Science

Brooke Grindlinger, PhD

The New York Academy of Sciences

Keynote Speaker

Daniel D. Bikle, MD, PhD

University of California, San Francisco and VA Medical Center
e-mail | website | publications

Daniel D. Bikle is a professor of medicine and dermatology at the University of California, San Francisco and co-director of the Special Diagnostic and Treatment Unit of the San Francisco VA Medical Center. He has a long history in the area of vitamin D, performing a number of the initial studies in its metabolism in the kidney and more recently its extrarenal metabolism in the skin. Much of Bikle’s recent research has focused on the molecular mechanisms by which 1,25(OH)₂D and its receptor (VDR) regulate gene expression, in particular during normal epidermal differentiation, wound healing, and hair follicle cycling and on the pathologic changes underlying epidermal carcinogenesis. Bikle is also a practicing endocrinologist with particular interest in metabolic bone disease and has written extensively on the interface between the laboratory and clinic with respect to the implications of the recent research in vitamin D function and its impact on patient care.

Speakers

Ricardo Boland, PhD

Universidad Nacional del Sur, Argentina
e-mail | website | publications

Ricardo Boland is superior investigator of the National Research Council (CONICET) and director of the Biological Chemistry Laboratories at the Universidad Nacional del Sur, Argentina. Boland obtained his PhD in biochemistry at the University of Missouri–Columbia. He completed postdoctoral training at St. Louis University School of Medicine and the Max-Planck Institute for Medical Research. He served as president of the Argentinean Societies for Biochemistry and Molecular Biology and Bone and Mineral Research. Boland’s research career has been mainly focused on the actions of vitamin D₃ on skeletal muscle functions. His major contributions are the identification of the vitamin D receptor (VDR) in this tissue; the characterization of signal transduction pathways involved in the regulation of the Ca2+ messenger system and myogenesis by 1,25(OH)2-vitamin D₃; and the demonstration of a functional role of the VDR in these events.

Sylvia Christakos, PhD

UMDNJ–New Jersey Medical School
e-mail | website | publications

Sylvia Christakos is a professor of biochemistry and molecular biology and at the University of Medicine and Dentistry of New Jersey (UMDNJ)–New Jersey Medical School. Christakos received her PhD from the State University of New York (SUNY) at Buffalo School of Medicine. She completed her postdoctoral training at the Roswell Park Memorial Institute, SUNY Buffalo School of Medicine, Department of Biochemistry and at the University of California at Riverside, California, Department of Biochemistry. Christakos has received continuous funding from the National Institutes of Health (NIH) and National Science Foundation (NSF) for the past 30 years. Her laboratory combines studies related to the functional significance of vitamin D target proteins using animal models with studies related to the molecular mechanism of 1,25(OH)₂D₃ action.

Luigi Ferrucci, MD, PhD

National Institute on Aging
e-mail | website | publications

Luigi Ferrucci is a geriatrician and an epidemiologist who conducts research on the causal pathways leading to progressive physical and cognitive decline in older persons. Ferrucci has made major contributions in the design of many epidemiological studies conducted in the U.S. and in Europe, including the European Longitudinal Study on Aging, the “ICareDicomano Study,” the AKEA study of Centenarians in Sardinia, and the Women’s Health and Aging Study. He was also the principal investigator of the InCHIANTI study, a longitudinal study conducted in the Chianti geographical area (Tuscany, Italy), which looked at risk factors for mobility disability in older persons. Ferrucci has refined the design of the Baltimore Longitudinal Study of Aging to focus more on normal aging, age-associated frailty, and factors associated with exceptionally healthy aging and longevity.

David G. Gardner, MD

University of California, San Francisco
e-mail | website | publications

David G. Gardner received an MS in biochemistry and an MD from the University of Rochester. He completed his residency training in Internal Medicine at the Massachusetts General Hospital before moving to the NIH to complete his fellowship in the Combined Endocrinology Training Program. He is the Mount Zion Health Fund Distinguished Professor of Medicine and chief of the Division of Endocrinology and Metabolism at the University of California, San Francisco. His research interests are concentrated in cardiovascular endocrinology, particularly on the regulation of cardiovascular and renal function by vitamin D.

Martin Hewison, PhD

University of California, Los Angeles
e-mail | website | publications

Lily Li

Mount Sinai School of Medicine

Lily Li is a third-year medical student at the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University. Li completed a one-year post-baccalaureate Intramural Research Training Award Program in immunology at the National Institutes of Health. She is currently pursuing a one-year Doris Duke Clinical Research Fellowship at the Mount Sinai School of Medicine.

Anastassios G. Pittas, MD

Tufts Medical Center
e-mail | website | publications

Anastassios G. Pittas is an associate professor of medicine at Tufts University School of Medicine, an adjunct associate professor of nutrition and policy at Tufts University Friedman School of Nutrition, Science, and Policy, and a center scientist at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University. He received his MD from Cornell University Medical College, completed his residency at the New York Presbyterian Hospital, and completed a fellowship in endocrinology at Tufts Medical Center before joining the Division of Endocrinology, Diabetes, and Metabolism at Tufts Medical Center. Pittas is the co-director of the Gerald J. and Dorothy R. Friedman New York Foundation for Medical Research Diabetes Self-education Program and the associate director of the Endocrinology Fellowship program. Pittas also holds an MS in clinical research from Sackler School of Biomedical Sciences at Tufts University.

Erica Rutten, PhD

Ciro +, Centre of Expertise for Chronic Organ Failure
e-mail | website | publications

Erica Rutten holds a PhD from Maastricht University in Maastricht, the Netherlands, where she studied amino acid metabolism in patients with chronic obstructive pulmonary disease (COPD). At the Center of Expertise for Chronic Organ Failure (CIRO+) in Horn, the Netherlands, she leads research on body composition, nutrition, and metabolism. Rutten received a research grant from the Dutch Asthma Foundation in 2008. Her interests include malnutrition in COPD, obesity, osteoporosis, vitamin D, and nutritional intake in patients with chronic disease.

Igor N. Sergeev, PhD, DSc

South Dakota State University
e-mail | website | publications

Igor N. Sergeev has over 25 years of experience in academic research in biochemistry and nutrition. Sergeev received his PhD from the Institute of Biomedical Problems and a DSc from the Institute of Nutrition, both in Moscow, Russia. As professor of nutritional sciences at South Dakota State University, he directs research program in nutritional biochemistry and molecular nutrition. Sergeev achieved international acclaim for his work on vitamin D metabolism, vitamin D receptors, and calcium signaling. In the last decade, he has been recognized for his research on the role of cellular calcium and vitamin D in the regulation of apoptosis.

Carol L. Wagner, MD

Medical University of South Carolina
e-mail | website | publications

Nicholette Zeliadt

Nicholette Zeliadt resides Washington, D.C., where she writes about science for scientists and non-scientists alike. She has a background in biochemistry and nutrition, and a PhD in environmental health sciences from the University of Minnesota. In pursuit of science, she has traveled by ship to the South Pacific Gyre, traversed the Willamette Valley by bike, and encountered 12 of the planet’s 13 climatic zones. She has written for Scientific American, Proceedings of the National Academy of Sciences, BioTechniques, and About.com.

Resources

Sylvia Christakos

Raghuwanshi A, Soshi SS, Christakos S. Vitamin D and multiple sclerosis. J Cell Biochem. 2008;105(2):338-43.

Dhawan P, Wieder R, Christakos S. CCAAT enhancer-binding protein alpha is a molecular target of 1,25dihydroxyvitamin D₃ in MCF-7 breast cancer cells. J Biol Chem. 2009;284(5):3086-95.

Christakos S, Ajibade DV, Dhawan P, et al. Vitamin D: metabolism. Endocrinol Metab Clin North Am. 2010;39(2):243-53.

Christakos S, DeLuca HF. Minireview: Vitamin D: is there a role in extraskeletal health? Endocrinology. 2011;152(8):2930-6.

Joshi S, Pantalena LC, Liu XK, et al. 1,25-dihydroxyvitamin D(3) ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A. Mol Cell Biol. 2011;31(17):3653-69.

Martin Hewison

Hewison M, Freeman L, Hughes SV, et al. Differential regulation of vitamin D receptor and its ligand in human monocyte-derived dendritic cells. J Immunol. 2003;170(11):5382-90.

Liu NQ, Hewison M. Vitamin D, the placenta and pregnancy. Arch Biochem Biophys. 2012;523(1):37-47.

Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311(5768):1770-3.

Liu N, Nguyen L, Chun RF, et al. Altered endocrine and autocrine metabolism of vitamin D in a mouse model of gastrointestinal inflammation. Endocrinology. 2008;149(10):4799-808.

Fabri M, Stenger S, Shin DM, et al. Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. Sci Transl Med. 2011;3(104):104ra102.

Hewison M. An update on vitamin D and human immunity. Clin Endocrinol (Oxf). 2012;76(3):315-25.

David G. Gardner

Chen S, Gardner, DG. Liganded vitamin D receptor displays anti-hypertrophic activity in the murine heart [published online ahead of print Sep 16 2012]. J Steroid Biochem Mol Biol. 2012.

Chen S, Law CS, Grigsby CL, et al. Cardiomyocyte-specific deletion of the vitamin D receptor gene results in cardiac hypertrophy. Circulation. 2011;124(17):1838-47.

Glenn DJ, Wang F, Nishimoto M, et al. A murine model of isolated cardiac steatosis leads to cardiomyopathy. Hypertension. 2011;57(2):216-22.

Chen S, Glenn DJ, Ni W, et al. Expression of the vitamin D receptor is increased in the hypertrophic heart. Hypertension. 2008;52(6):1106-12.

Carol L. Wagner

Hollis BW, Wagner CL. Vitamin D and pregnancy: skeletal effects, nonskeletal effects, and birth outcomes Study [published online ahead of print May 24 2012]. Calcif Tissue Int. 2012.

Wagner CL, Taylor SN, Dawodu A, et al. Vitamin D and its role during pregnancy in attaining optimal health of mother and fetus. Nutrients. 2012;4(3):208-30.

Hollis BW, Johnson D, Hulsey TC, et al. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res. 2011;26(10):2341-57.

Johnson DD, Wagner CL, Hulsey TC, et al. Vitamin D deficiency and insufficiency is common during pregnancy. Am J Perinatal. 2011;28(1):7-12.

Hamilton SA, McNeil R, Hollis BW, et al. Profound vitamin D deficiency in a diverse group of women during pregnancy living in a sun-rich environment at latitude 32°N. Int J Endocrinol. 2010;2010:917428.

Igor N. Sergeev

Song Q, Sergeev IN. Calcium and vitamin D in obesity. Nutr Res Rev. 2012;25(1):130-41.

Sergeev IN. 1,25-dihydroxyvitamin D₃ induces Ca2+-mediated apoptosis in adipocytes via activation of calpain and caspase-12. Biochem Biophys Res Commun. 2009;384(1):18-21.

Sergeev IN. Calcium as a mediator of 1,25-dihydroxyvitamin D₃-induced apoptosis. J Steroid Biochem Mol Biol. 2004;89-90(1-5):419-25.

Pittas AG, Dawson-Hughes B, Li T, et al. Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes Care. 2006;29(3):650-6.

Ricardo Boland

Boland RL. VDR activation of intracellular signaling pathways in skeletal muscle. Mol Cell Endocrinol. 2011;347(1-2):11-6.

Buitrago C, Costabel M, Boland R. PKC and PTPα participate in Src activation by 1α,25OH2 vitamin D₃ in C2C12 skeletal muscle cells. Mol Cell Endocrinol. 2011;339(1-2):81-9.

Buitrago C, Boland R. Calveolae and caveolin-1 are implicated in 1alpha,25(OH)2-vitamin D₃-dependent modulation of Src, MAPK cascades and VDR localization in skeletal muscle cells. J Steroid Biochem Mol Biol. 2010;121(1-2):169-75.

Luigi Ferrucci

Mai X-M, Chen Y, Camargo CA Jr, Langhammer A. Cross-sectional and prospective cohort study of serum 25-hydroxyvitamin D level and obesity in adults: the HUNT study. Am J Epidemiol. 2012;175(10):1029-36.

Shardell M, D’Adamo C, Alley DE, et al. Serum 25-hydroxyvitamin D, transitions between frailty states, and mortality in older adults: the Invecchiare in Chianti Study. J Am Geriatr Soc. 2012;60(2):256-64.

Semba RD Chang SS, Sun K, et al. Serum 25-hydroxyvitamin D and pulmonary function in older disabled community-dwelling women. J Gerontol A Biol Sci Med Sci. 2012;67(6):683-9.

Ferrucci L, Studenski S. Clinical Problems of Aging. In: Longo D, Fauci A, Kasper D, Hauser S, Jameson J, Loscalzo J, eds. Harrison’s Principles of Internal Medicine, 18th ed. New York, NY: McGraw-Hill; 2011:570-588.

Llewellyn DJ, Lang IA, Langa KM, et al. Vitamin D and risk of cognitive decline in elderly persons. Arch Intern Med. 2010;170(13):1135-41.

Visser M, Deeg DJ, Lips P, et al. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab. 2003;88(12):5766-72.

Daniel D. Bikle

Rosen CJ, Adams JS, Bikle DD, et al. The nonskeletal effects of vitamin D: an Endocrine Society scientific statement. Endocr Rev. 2012;33(3):456-92.

Ross AC, Taylor CL, Yaktine AL, Del Valle HB, eds., Committee to Review Dietary Reference Intakes for Vitamin D and Calcium, Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press; 2010.

Bikle D. Nonclassic actions of vitamin D. J Clin Endocrinol Metab. 2009;94(1):26-34.

Newhook LA, Sloka S, Grant M, et al. Vitamin D insufficiency common in newborns, children and pregnant women living in Newfoundland and Labrador, Canada. Matern Child Nutr. 2009;5(2):186-91.

Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med. 2009;169(6):551-61.

Nutrition on a Global and Local Scale

Rafael Pérez-Escamilla works to create and implement public health nutrition programs around the world, but realizes that effective programs must take both a global and local view.

Published June 1, 2012

By Marci A. Landsmann

Image courtesy of bit24 via stock.adobe.com.

“Good health” is more than a fortuitous platitude; a nutritious diet can help humans plot the course to lifelong wellness—a fact not lost to scientists and public health experts.

But despite efforts of governments and international organizations to equitably provide nutritious food supplies, more than 2 billion people worldwide are still malnourished. Working to further understand the variables at play, Rafael Pérez-Escamilla, professor of epidemiology and public health and director, Office of Community Health, Yale School of Public Health, has spent his career elucidating the roots of nutrition inequities—in addition to paving the way for practical solutions.

“Of course, it’s important to understand the mechanisms of nutrition at the molecular and cellular levels,” Pérez-Escamilla says. “But on the other hand, we have to be able to translate the vast knowledge that we now have into effective public health programs and there is a science to this too.”

Pérez-Escamilla has used the precision of science to track the impact of food insecurity in Brazil. His efforts started on a small scale with an experience-based household survey of some 120 households in the city of Campinas, which quickly grew into a national project. This major undertaking has not only helped the Brazilian government target and monitor the impact of its hunger eradication programs but has also allowed researchers to identify the causes of food insecurity and how this condition affects human development.

Improving Food Security Governance

Since being put into wide-scale use in Brazil, as well as Colombia and Mexico, the United Nations Food and Agricultural Organization has been disseminating the Latin America and Caribbean Food Security Scale, developed under the leadership of Pérez-Escamilla and colleagues, as a standard for the entire region. This is a major step forward for improving food security governance, as the scale allows key stakeholders to accurately measure strides in their efforts against household food insecurity and malnourishment.

“It’s fundamental to be able to compare progress across countries but also for countries to have simple but valid measures that they can trust and build policies around,” says Pérez-Escamilla. With funding from The Bill & Melinda Gates Foundation, Pérez-Escamilla has also recently led the development of a breastfeeding scale up model that encourages new mothers to breastfeed.

Exclusive breastfeeding for six months is one of the most cost-effective maternal-child health interventions, but many barriers have prevented the successful promotion of this optimal infant feeding behavior on a global scale. Pérez-Escamilla aims to overcome these barriers with well-coordinated, intersectoral strategies that engage new mothers in health facilities as well as in community settings.

A Goal to Help All

Whether analyzing the best way to promote breastfeeding or crafting metrics to realistically paint pictures of household food insecurity and malnutrition around the world, Pérez-Escamilla’s goal is to help “all people at all times to have access to sufficient, safe, nutritious food to maintain a healthy and active life.”

This seemingly simple definition of food security, crafted at the World Food Summit in 1996, provides an ideal expectation but in no way drafts a map to that end Understanding Household Food Insecurity Less-developed countries are increasingly inheriting some of the nutritional problems of more developed countries, largely because of the adoption of Western diets and lifestyles. For example, rates of overweight/obesity in some countries in Latin America and the Caribbean are now comparable to those in the United States, Pérez-Escamilla points out.

“In middle income countries food insecurity at the household level is not really related as much to food quantity anymore as it is to dietary quality. A low quality diet among the poor is often times the result of lack of economic or physical access to nutritious foods such as fruits and vegetables and easy access to highly caloric, unhealthy foods,” says Pérez-Escamilla. This reflects the alarming increases in obesity among the poor in these countries.

“Sadly, little is being done to try to apply lessons learned from countries more advanced in this nutrition transition to prevent the same outcome from happening in areas where the transition is less advanced, as in Sub-Saharan Africa. I believe addressing this gap should be a major global health focus.”

Developed Countries Not Immune

In addition, Pérez-Escamilla has learned that people in developed countries are not immune to nutrition-related health inequities. This motivated him to lead a National Institutes of Health-funded study examining the impact of community health workers at improving behavioral, metabolic, and health outcomes among Latinos with Type 2 diabetes in the United States.

“When I came to Connecticut in the early ‘90s and learned about the major health inequities affecting Latinos in the wealthiest state in the country, I decided to reconsider the single focus of my work in developing countries,” says Pérez-Escamilla. “As soon as I started doing this work, I realized how common the root of health inequities is regardless of geographical location. The root is what we now refer to as ‘the social determinants of health’ that calls for well-integrated, multi-level and multi-sectoral solutions developed and governed in strong partnership with affected communities.”

Just as systems biology analyzes the interplay between biological systems, the problems of malnutrition and global health are also complex. “Global health is local health. I understand global as a complex system and local as the cells that form the system. As a result of globalization, local communities, or the cells, are strongly interlinked with each other both within regions and countries and across countries and global macroregions,” says Pérez-Escamilla.

“If the architecture of global health governance continues to be fundamentally inequitable, then the ultimate global health goal of attaining ‘health for all’ regardless of where a human being is born becomes impossible to achieve.”

About the Author

Marci A. Landsmann is a medical writer in Philadelphia.

Expert on HIV/AIDS Appointed to Advisory Group

A young child gets blood drawn by a medical professional.

Academy member Chinua Akukwe answers the “call to duty” as he uses his public health expertise to combat the spread of HIV/AIDS, specifically in Africa.

Published April 16, 2012

By Diana Friedman

Chinua Akukwe, professorial lecturer in the Departments of Global Health and Prevention and Community Health in the George Washington University (GWU) School of Public Health and Health Services and former chair of the Technical Advisory Board of the GWU Africa Center for Health and Human Security, has been appointed to the independent Global Advisory Group on Funding Priorities for UNITAID. UNITAID is dedicated to scaling up access to treatment for HIV/AIDS, malaria, and tuberculosis by leveraging price reductions for quality diagnostics and medicines and accelerating the pace at which these are made available. Since 2006, UNITAID has committed over U.S. $1.5 billion to support projects in 94 countries.

“This appointment is a call to duty during one of the most important periods in global health and financing for international development,” says Akukwe. “UNITAID, with its focus on innovative mechanisms for scaling up access to medicines and other public health goods, can play a more significant role in leveraging scarce resources to reach more individuals and families in need,” he adds.

Akukwe is an expert on the global response to HIV/AIDS, with a particular focus on Africa. He developed the “Communicable Diseases Guidelines” of the Africa Development Bank that established HIV/AIDS, malaria, and tuberculosis as priority health conditions. He also developed the “Strategic Framework for the Implementation of Universal Access to HIV/AIDS, Malaria and Tuberculosis” for the African Union Commission, which was subsequently approved by the African Council of Health Ministers.

Also read: A New Approach to Treating HIV/AIDS in Iran

Scientific Community Mourns Fleur L. Strand

The cover of a science report titled: Models of Neuropeptide Action.

The neuroscientist and former Academy board chair broke scientific and social ground throughout her long career.

Published January 11, 2012

By Diana Friedman

Fleur L. Strand, a physiologist who was a pioneer of the neuropeptide concept, died of cancer on December 23, 2011, in her home in Snowmass Village, Colorado. She was 83.

Strand was actively involved in The New York Academy of Sciences throughout her career, being named a Fellow in 1976 and being elected as chair of the board in 1987. Both her leadership and her friendship will be missed by the Academy community.

Most recently, Strand held the title of Carroll and Milton Petrie Professor of Biology and Professor of Neural Science, Emerita, at New York University (NYU), where she retired in 1997. After her retirement, she was appointed by Governor George Pataki to the New York State Spinal Injury Research Board in 2001 and served as a consultant for several pharmaceutical companies until 2010.

Throughout Strand’s illustrious career, which began at NYU, where she received her BA, MS, and PhD degrees, she broke new ground, both in research and the role of women in science. In 1957, she received a National Institutes of Health postdoctoral fellowship to study at the Physiological Institute of the Free University in Berlin, Germany. During these early years of research, Strand was the first to show that stress-evoked hormones could have a direct effect on the peripheral nervous system, independent of the classical role of the adrenal gland. It took a number of years for the scientific community to accept the concept of neuropeptides.

First Female Department Chair

Following her postdoctoral research in Berlin, Strand returned to NYU in 1961 and was appointed to a faculty position in the Biology Department. In 1980, she became the first female chair of the department. Strand remained an active researcher in the field of neuropeptides, as well as a beloved teacher and mentor, at NYU for 36 years. During this time, Strand sponsored more than 80 graduate student dissertations, authored multiple textbooks and primary research and review articles, and co-founded several professional societies, including the International Neuropeptide Society.

In her personal life, Strand enjoyed a long marriage to her husband of 65 years, Curt Strand. Curt Strand is a retired CEO of Hilton International. The couple enjoyed many years of vacationing in Snowmass Village, Colorado, before moving there full-time in 2004. A memorial celebration for Strand will be held on February 24 at the Snowmass Club.

Also read: Remembering Former Academy Borad Member Jim Simons

Why Good Science Resists Characterization

“Science is an adventure; it’s the human search for knowledge and new ideas that can better humankind.”

Published December 1, 2011

By Marci A. Landsmann

Image courtesy of amorn via stock.adobe.com.

Science is a discipline that whittles the abstract into clear and precise terms. So it might seem odd, at first, that Elias Zerhouni, former director of the National Institutes of Health and esteemed scientist, takes issue with certain characterizations.

“I don’t like to call something, ‘basic science’ or ‘translational science,’” says Zerhouni, a member of the Academy President’s Council. “It’s either good science or bad science. I don’t think we should characterize any type of science. Science is an adventure; it’s the human search for knowledge and new ideas that can better humankind. To pigeonhole types of science is, in my view, not beneficial.”

Definitions can create barriers, says Zerhouni. And he has spent his life stepping over such lines, first in academia at Johns Hopkins, then at the National Institutes of Health, and now in private industry in his recently assumed role as president of global research and development at Sanofi-Aventis.

In the early days of Zerhouni’s career as a radiologist at Johns Hopkins, he recalls not being able to secure NIH funding for his own research, because it didn’t fit neatly into a single disease process or under the purview of one single NIH institute. It took private industry funding to make his proposed research path—which years later led to imaging technologies that could show the heart in three dimensions and help clinicians decipher between cancerous and noncancerous nodules in the lungs—a reality.

Funding Reform

Zerhouni got the opportunity to make changes in the way the NIH chooses and awards research grants when he was appointed NIH director. He assembled a multidisciplinary team and a “Roadmap for Medical Research,” which isolated areas of science that would most benefit from cross-collaboration. The NIH Reform Act of 2008 established the NIH’s Common Fund, specifically for research that involves at least two of the 27 institutes in the NIH. In addition, it also set up funds for the Pioneer Award, which supports individual scientists of exceptional creativity who propose pioneering, and possibly transforming, approaches to major challenges in biomedical and behavioral research, despite not fitting neatly into a single disease category.

“You need a diversity of approaches,” Zerhouni says. “Sometimes funding agencies use a one-size-fits-all approach, which doesn’t help the real nature of science, which can go from the proverbial single investigator in the lab doing fundamental observation…to having the ability to put together teams to understand computational biology and bioinformatics. So in my view, the funding agency should reflect the realities of science and not the other way around.”

During his time at the NIH, Zerhouni encouraged further collaboration between scientists by creating multi-principal investigator grants, which allowed each scientist on a project to have lead investigator status. “Under a single lead investigator system, everybody else would be secondary. Well, that, in some way, discourages collaboration because everyone wants to be recognized in their own field as the top scientist.” The multi-PI grant gave scientists equal billing to contribute to the scientific problem at hand—and to converge in the same way as science does.

Matter of Perspective

Zerhouni attributes his success, in part, to his own unique background. Algerian-born, Zerhouni came to America when he was 24, after securing a residency at Johns Hopkins. He quickly learned the role perspective can play in the world of medicine.

“I think maybe part of my ability to succeed here is that I can bring a viewpoint that many people feel is sometimes surprisingly different and constructive in showing there is a different way,” says Zerhouni. “I think being an immigrant enriches the mix.” He applauds the U.S. for welcoming scientific immigrants and their contributions, pointing out that science is the great peacemaker.

Zerhouni cites the fact that 30% of all Nobel Peace Prizes in Medicine have been won by immigrant Americans. “No country has all of the talent to overcome its problems and that’s why I think science has to be global, it has to be without artificial barriers, and we should encourage collaboration and self-assembly wherever it comes from, provided that it is good science.”

About the Author

Marci A. Landsmann is a medical writer in Philadelphia.

Advancing the Science of Personalized Cancer Medicine

Academic and industry researchers, technology developers, and clinicians discuss the progress and the challenges in the field of personalized cancer medicine.

Published December 1, 2011

By Jamie Kass

Personalized medicine, the treatment of patients based upon their individual genetic, epigenetic, and phenotypic makeup, is the ultimate goal of many researchers and clinicians trying to find less toxic and more effective therapies for cancer. While cancer as a whole is characterized by uncontrollably proliferating cells, the disease is being subdivided into increasingly smaller units, from organ-specific to gene-specific categories.

An understanding of the molecular basis of some cancers and an increasing knowledge of how those cancers differ from those in other organs and in other individuals have led to the development of drugs enormously successful at treating those types of cancer. Yet many other candidate drugs based on the same kind of analysis fail in the clinic, leaving cytotoxic chemotherapy still the standard treatment for many patients.

From May 19-21 2010, academic and industry researchers, technology developers, and clinicians from around the world gathered in Barcelona, Spain, to discuss the progress and the challenges in the field of personalized cancer medicine. A special technology workshop highlighted the important role of technological advances in driving the efforts toward personalized medicine. Conference participants also discussed their concerns about the field, in particular the failure of the U.S. clinical trial system to keep up with the changes demanded by the new approach.

Researchers have made great progress in discovering the cellular processes that have become pathological in cancer. For example, it is clear that genetic and epigenetic changes that affect cell proliferation, DNA repair, programmed cell death, stem cell maturation or self-renewal, and other fundamental cellular and molecular activities can lead to cancer formation.

Systemic Problems, Clinical Medicine, and Technology

New information is also coming to light about more systemic problems, such as the survival of cancer cells in different microenvironments, the cells’ ability to stimulate angiogenesis, and the way they promote their own survival by interacting with noncancerous cells to acquire nutrients, suppress immune response, and meet other important needs. The most cutting-edge research in all of these areas was discussed by leading researchers in the field.

Moving toward clinical medicine, researchers discussed how oncogenomics and tumor profiling can reveal the signaling pathways mutated in a particular tumor type as well as the variability among tumors within that type. Breast cancer researchers are at the forefront of efforts to use gene expression signatures and other molecular data to guide treatment, predict risk, and understand epidemiological phenomena. There are several clinical trials underway to test some of these new tools, some of which were presented in talks about efforts to identify biomarkers for prognosis and treatment response.

The conference also delved into a variety of approaches to developing targeted therapies for cancer. Some of these efforts take advantage of technologies that allow high-throughput analyses of genomic information and drug responses in cell culture. Others use preclinical mouse models to evaluate candidate target therapies or to counteract the drug resistance that often thwarts cancer treatment. Next-generation sequencing and microarray technology have also played an important part in the advance toward personalized cancer medicine, as a technology workshop highlighted.

Also read: Advancing Cancer Research and Therapies

A Conversation with Napoleone Ferrara

“We want to know why, for example, not all tumors respond to vascular endothelial growth factor inhibitors. We want to understand resistance.”

Published December 1, 2011

By Diana Friedman

Napoleone Ferrara (center) receives the 2011 Dr. Paul Janssen Award for Biomedical Research with (left to right) Joaquin Duato (J&J), Craig Mello (University of Massachusetts Medical School; Howard Hughes Medical Institute), Harlan Weisman (J&J) and Paul Stoffels (J&J).

Napoleone Ferrar, a Genentech Fellow, discusses his life’s work: from discovering the core angiogenic signaling molecule, vascular endothelial growth factor (VEGF), to creating anti-VEGF therapeutics for wet age-related macular degeneration and cancerous tumors.

What motivated you to go into research?

I studied medicine in Catania, Italy, my hometown. Initially I thought that clinical medicine was very interesting, but I didn’t have a firm direction. Then, I met a professor of pharmacology with an established research group. I joined this group as a medical student and that’s what introduced me to research. It was thanks to my post-doctoral mentor at University of California, San Francisco, that I was able to further hone my research interests. Both of these people were very influential and inspirational factors.

Broadly, how did you identify VEGF and identify its role?

I was interested in endocrinology and neuroendocrinology. The pituitary is the master regulator of many key physiological processes. During my fellowship at UCSF, I stumbled on a population of pituitary cells without an established function. As part of my postdoctoral work, I tried to characterize these cells. I found that they released a factor that promotes angiogenesis. Over time I was able to isolate this molecule: I named it vascular endothelial growth factor (VEGF). After that, and through the work of a number of other labs, it became clear that VEGF is a very important signaling molecule.

As your work progressed, what were your biggest challenges in translating your discoveries to the development of therapeutics?

We were very fortunate that we found the right target but the challenge was proving that. Initially there was a lot of controversy about angiogenesis. There was skepticism about VEGF’s role in angiogenesis; people thought that maybe there were other molecules at work. We had to prove our findings through sound scientific methods.

What factors have contributed to your success?

I have a medical background even though I have not been a practicing physician for a long time. Perhaps that medical background helped me to guide my research into an area that is therapeutically relevant. I was also just very fortunate that the VEGF molecule turned out to be so important. Being at Genentech for 22 years helped push my work along. I think it would have been difficult to do the same work in a different setting.

You recently received the 2011 Dr. Paul Janssen Award for your breakthrough research on VEGF, and in 2010 you received the Lasker Award. What do these awards mean to you?

They express the fact that my peers, my colleagues, respect this work, so that means a lot to me personally. But the awards also reflect on the work that my group has done over the years. To me, these awards are really a stimulus to do more. I see them as motivation to do more and better research.

What are your biggest research priorities right now?

We’re trying to follow up on our work on VEGF. We want to know why, for example, not all tumors respond to VEGF inhibitors. We want to understand resistance. This will mean dissecting tumors to refine our understanding of angiogenesis. Regarding pro-angiogenic therapies, clinical studies thus far have been quite disappointing. It’s very difficult to reconstruct complex vessels to positively impact circulation. It would be really wonderful if someone could figure out how to do that.

This story originally appeared in the Fall 2011 issue of The New York Academy of Sciences Magazine.

The Role of Academic Medical Centers

Academic medical center must continue to bring together clinical and scientific resources, in the service of bettering humankind.

Published December 1, 2011

By Diana Friedman

“I don’t like the distinction between basic and translational science; science should be seamless,” says Laurie Glimcher, the Stephen and Suzanne Weiss Dean, Weill Cornell Medical College, effective January 2012. Many of her colleagues in the academic medical center community support Glimcher’s viewpoint.

“No matter what we call the discovery and development of new therapeutic drugs, it’s critical for the future of patient care that we focus on breakthroughs in therapeutics,” says Kenneth L. Davis, president and CEO, Mount Sinai Medical Center.

For Glimcher, who spends the majority of her professional life in a laboratory, her training as a physician still informs her desire to translate laboratory discoveries into viable clinical treatments. This is the quintessential mission of an academic medical center: to bring together clinical and scientific resources, with a greater duty of service to humankind. This mission is further supported by the Bayh-Doyle Act, a federal mandate that requires academic medical centers to develop discoveries at the bench into benefits for patients, notes Glimcher.

In order to move translation forward, clinicians and scientists must interact. “We need great clinicians who understand how to interface with laboratory scientists, we need scientists to ask research questions that are relevant to disease, and we need bridges that connect the two groups,” says David S. Stephens, vice president for research, Woodruff Health Sciences Center, Emory University. “This happens in academic medical centers, but it doesn’t happen well in all of them.”

Medical Model of Choice

“We have never lived in a time when opportunities were greater in biomedical research,” says Davis. And, as pharmaceutical interests increasingly move from discovery to development, academic medical centers must play a leading role in seizing these opportunities.

Jeffrey Bluestone, executive vice chancellor and provost, University of California, San Francisco (UCSF), believes that one way to greatly increase translation is to focus “our incredible science on humans as the complex medical model of choice.”

“To me, one of the most exciting post-human genome and technology advancements is thinking about the human organism as a place to do cutting-edge research, just like mice were our organism of choice in the past.” To do that, says Bluestone, academic medical centers will need to engage faculty and students in areas of human biology while improving existing infrastructure (data and tissue banks, bioinformatics technology, etc.) so that it is up to the task of human research.

Incentives Needed

Despite the incredible research opportunities afforded by an increase in scientific knowledge, academic medical centers face many challenges that make the realization of translation an uphill climb. Declining Medicare and Medicaid reimbursement leads to clinicians with packed patient schedules, leaving less time for vital collaboration with laboratory-based scientists, who are themselves faced with a dearth of research funds.

“Ninety-three percent of grants are turned down. A basic scientist will write their best grant in the area with which they are most comfortable and often that isn’t an area of disease,” says Davis. This underscores a critical need in academic medical centers: finding ways to incentivize both laboratory-based scientists and clinicians to spend more time working together and, ultimately, to make progress in creating new therapeutics for disease.

Many academic medical centers are providing incentives on an institutional level, by investing large amounts of financial and organizational resources to create physical spaces that support the day-to-day process of translation. For example, new buildings are being created at Weill Cornell Medical College and Mount Sinai Medical Center to foster closer collaboration between clinicians and laboratory-based scientists, blurring the lines between such disciplines to create the ‘seamless science’ of Glimcher’s vision.

Putting scientists and clinicians from diverse disciplines and backgrounds in close proximity to each other is useful both for its practicality and its ability to drive culture change. “Many of our faculty are used to, and very successful at, working independently or with a few collaborators,” says Bluestone. “We need to find ways to allow faculty to overcome barriers to communication and collaboration.” Having a building where scientists, clinicians, and students with varying degrees and areas of expertise work side-by-side is one way to facilitate a free exchange of information and ideas.

Reaching Out

In addition to new initiatives that pool intra-institutional resources, partnerships between academic medical centers are key, says Glimcher. “Here in New York, we have the so-called four corners—New York Presbyterian, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, and The Rockefeller University. We all have unique strengths, so we want to leverage those to avoid duplicating efforts. It’s more cost effective.”

At the Atlanta Clinical & Translational Science Institute (ACTSI), partnerships span three academic institutions—Emory University, Morehouse School of Medicine, and Georgia Institute of Technology—as well as a variety of health care and non-profit partners. All of these organizations pool resources “to rapidly and efficiently translate scientific discoveries to impact all populations of the Atlanta community,” says Stephens, who is the institute’s principal investigator.

Often, the results of these initiatives reach well beyond Atlanta. For example, ACTSI scientist Bali Pulendran recently published a systems biology approach to determine innate and adaptive responses to influenza vaccination, providing a new platform to predict vaccine immunogenicity and establishing new mechanistic insights for vaccine development.

Educating the Educators

Another way to incentivize both scientists and clinicians to expend more time and professional resources on the development of disease-modifying compounds is to provide professional education that emphasizes the skills necessary for translation. Some schools now offer master’s degrees in clinical sciences or translational science, in which physicians learn to become clinical researchers.

UCSF, a health sciences campus, recently developed ties with a local law school to help researchers learn about issues such as conflict of interest and consent forms. And ACTSI hosted a forum, in partnership with industry, to teach laboratory-based scientists about the process of creating a therapeutic product—an area most of those in attendance had never learned about before.

Such ties with industry are vital to avoiding the so-called valley of death—that stage where development of a previously promising compound languishes and dies—says Bluestone. “We need a different model of partnership with industry. Not one where industry licenses a drug from us and they tell us to go away, or one where industry provides us with money to do research and we tell them to go away.” At UCSF, Pfizer locates full-time scientists on the university campus, leading to greater interaction and better understanding of both sides of the process—discovery and development.

Industry collaboration is incredibly valuable, agrees Glimcher, provided there is full transparency from all sides. “In the olden days, basic scientists looked down on clinical researchers,” says Glimcher. “It’s not so different from how academics used to perceive industry. I believe those distinctions are largely being erased. Many of my esteemed colleagues have crossed over from academia to industry and vice versa. I think that’s a positive thing, so long as there’s transparency.”

A Unique Advantage

Indeed, collaboration, both within and outside of academia, is necessary to overcome translational hurdles. The potential rewards are great. But, says Bluestone, academic medical centers do not have to look beyond the borders of their campuses to find two of their most valuable resources: students and patients.

“Our students are tremendous resources that drive innovation and creativity,” says Bluestone. “They can help us challenge the status quo.”

At ACTSI, researchers interact regularly with community boards, set up to provide a forum for two-way communication and to engender trust between community members/patients and the institute. “The community boards allow us to reach out to communities about our research projects, but they also allow communities to contribute to us by telling us about their unmet clinical needs,” says Stephens.

Targeting research, and subsequent drug development, to unmet health needs is perhaps the best example of how academic medical centers can make a real-life difference through translation.

Also read:

A Medical Education Paradigm for the Future

A man in a suit and tie smiles for the camera.

George Thibault and the Josiah Macy Jr. Foundation help the Academy push progress around medical education for the public good.

Published September 1, 2011

By Noah Rosenberg

George Thibault knows as well as anyone that medicine is an ever-evolving frontier, continuously fraught with new challenges that demand innovative solutions. In fact, Thibault, president of the Josiah Macy Jr. Foundation and an Academy governor, is the first to admit that his medical school education at Harvard would, by itself, be insufficient in today’s medical world.

“Health care professionals,” he says, “now need different kinds of experience to prepare them for a very different world than the one I was prepared for when I finished my training.”

Thibault stresses that the health care system evolves so quickly that current health care professional training, in certain respects, is often obsolete by the time a graduate enters his or her chosen field. Factors such as the diversification of patient demographics, the rise of chronic disease, and the shift in care delivery from hospitals to community-based interventions make for a model in flux.

“Educational programs,” he insists, “need to catch up with those changes.”

Thibault and the Josiah Macy Jr. Foundation, recently partnered with The New York Academy of Sciences (the Academy) to create the Translational Medicine Initiative. A three-year partnership that began in early 2010, the initiative fosters discussion and collaboration among physicians and basic researchers, industry and academic scientists, and public health experts, among others in the medical arena. The goal is to enable participants to learn from recent scientific breakthroughs, receive career development in translational medicine, and, ultimately, decrease the time needed to convert basic science into clinical applications.

Shaping the Future of Science

The partnership is accomplishing nothing less than helping to “shape the future education, research, and clinical care practices of thousands of physicians, scientists, and educators around the globe.” This is achieved through programs like the Translational Medicine Discussion Group—a forum for distributing information to the larger scientific and medical communities—and partnership-sponsored Academy memberships for medical school students and clinical fellows, which expose them to cutting-edge discoveries and enhance their delivery of care. Additionally, the Translational Medicine Initiative, whose findings are disseminated via simulcast webinars, multimedia eBriefings, podcasts, and articles in Annals of the New York Academy of Sciences, grants students access to the Academy’s Science Alliance events, which provide non-traditional career development opportunities.

The Translational Medicine Initiative, Thibault says, goes hand in hand with The Macy Foundation’s simple yet lofty goal: improving the health of the public through improving health professional education, a philosophy that was at the core of Thibault’s esteemed career as a Harvard physician and educator. He spent more than 40 years with the university, in posts including founding director of the Academy at Harvard Medical School and chief medical officer at Brigham and Women’s Hospital, and he has brought his educational values and beliefs with him to The Macy Foundation.

“We’re not abandoning what we’ve done before,” Thibault says of progress in the industry, “but we need to do more and improve upon it for this different health care system, delivery system, and patient population.”

“We’re building on the excellence of the past but adapting it to a changing world,” he says.

Creating a Healthier Society through Empowerment

After all, Thibault explains, the irony of medical training is that physicians traditionally spend most of their education alongside classmates in their particular specialty as opposed to those in complimentary fields with whom they will spend most of their careers.

“We think more of the educational process should be learning with and from other health professionals,” he says, noting that The Macy Foundation has received commitments from more than 15 schools and six major professional societies—including nursing and medicine— who recognize the importance of making joint-curriculum planning “the educational paradigm for the future.”

At the end of the day, however, Thibault is careful to note that while The Macy Foundation’s strategy has certainly adapted over the years, its core mission is as strong as ever: creating a healthier society by empowering the professionals who live and breathe medicine. “We don’t have enough resources ourselves to bring about the changes we want to see,” Thibault says, “so a large part is communicating ideas and getting others to pick up ideas. Ultimately, we have to go beyond what we alone as a foundation can do.” The Translational Medicine Initiative does just that, lending Academy resources to The Macy Foundation’s mission.

Also read: The Role of Academic Medical Centers

About the Author

Noah Rosenberg is a journalist in New York City.

Bringing Translational Science to the Silver Screen

From the research lab to the movie set, Columbia University’s W. Ian Lipkin lends his public health expertise to the pandemic thriller Contagion.

Published September 1, 2011

By Diana Friedman

W. Ian Lipkin at the New York City premiere of *Contagion* on September 7, 2011. Photo courtesy of Dave Alloca via Starpix.

W. Ian Lipkin, The John Snow Professor of Epidemiology at Columbia University’s Mailman School of Public Health, recently found himself mentoring a new kind of student—the Hollywood variety. Lipkin, also director of the Center for Infection and Immunity, served as senior technical advisor for Contagion, the pandemic thriller released in September 2011. The advising process started three years earlier, when the Academy member was recruited to work on the big-budget film.

**Why did you sign on as an advisor for Contagion?**

I had been asked to review movies in the past and most of the time, my reviews were negative. This was the first time I signed on to help in the creation of a movie. I was very impressed with the screenwriter, Scott Z. Burns, because he came to this with no preconceived notions. Both Scott and the director, Steven Soderbergh, were committed to a strong scientific foundation (incidentally, they’re both kids of academics, so they grew up in that tradition).

Additionally, the movie provided a unique opportunity to educate millions of viewers about the challenges—scientific, political, economic, logistical, and humanistic—of emerging infectious diseases, and the opportunities we have to address them.

How does the topic of the movie relate to what you do on a daily basis?

Our Center is known for its work in pathogen discovery, surveillance, diagnostics, and immunotherapeutics. We have programs in the developing world, including one focused on the Nipah virus, the inspiration for the virus in the film.

In which aspects of the movie-making process were you involved?

I presented several scenarios for the pandemic, and recommended the one that was selected. Thereafter, Craig Street, a bioinformatician at the Center for Infection and Immunity, and I designed the virus by downloading existing viral sequences from a GenBank database and stitching them together. We then created three dimensional virus models based on structures of Nipah and Hendra, which were solved by Bowden and colleagues at Oxford, and described its evolution over the course of the pandemic.

I also helped with dialogue; made suggestions for props, set, makeup, and costume design; helped to train actors in the specifics of laboratory work; and connected the crew and cast to laboratory and public health scientists for expertise and insights I could not provide. We also recorded portions of the soundtrack at Columbia—biocontainment doors opening and closing, whirring centrifuges, cages rolling down hallways.

Do you feel that the finished movie accurately represents the work of an infectious disease scientist?

Consultants don’t, nor should they, have control of the finished work. Nonetheless, I am pleased with the outcome and the feedback from my colleagues has been positive too.

There are minor issues like the time from virus discovery to having a vaccine might be six months rather than four, or that the incubation period is too short. But by and large, the movie is scientifically plausible. Furthermore, it shouldn’t take six months to make and distribute a vaccine. We can do better.

How does this film address the issue of translational science?

In this film, we’re trying to engender interest in supporting translational work: developing vaccines, drugs, and diagnostics to reduce the impact of disease.

We think this film is timely because there is a threat to science funding at all levels: state, federal, and global. This film makes the case for why it’s important to not only maintain support, but increase it. The risks are too great.

What are your biggest professional priorities when faced with a new microbial threat?

I start out with a series of questions: What is it? Where did it come from? How is it transmitted? What does it do and how? Where is it going? Is it stable or is its pathogenicity changing? Is everyone equally vulnerable, and if not, why not?

My action items include answering the questions, building and implementing diagnostic tools for clinical management and surveillance, and establishing countermeasures.

Also read: SARS: An Emerging Infectious Threat and An Academy Member’s Work in Prime Time

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Overview

Speakers

Sponsors

Introduction

Keynote Speaker

Highlights

Synthesis and metabolism of vitamin D

Vitamin D mechanism of action

Keynote address: Vitamin D dietary reference intakes

Non-classical Roles of Vitamin D, Part 1

Speakers

Highlights

Vitamin D’s impacts on cancer and multiple sclerosis

Vitamin D in immune function and disease prevention

Vitamin D during pregnancy and lactation

Vitamin D and the cardiovascular system

Non-classical Roles of Vitamin D, Part 2

Speakers

Highlights

Vitamin D and apoptosis in obesity

Vitamin D and lung function

Vitamin D and chronic kidney disease

Policy and Clinical Applications

Speakers

Highlights

Vitamin D and type 2 diabetes

Vitamin D and muscle function

Vitamin D and Physical and Cognitive Function in Older Persons

Panel Discussion

Moderator

Open Questions

Speakers

Organizers

Heike Bischoff-Ferrari, MD, MPH

Martin Hewison, PhD

Nabeeha Mujeeb Kazi, MIA, MPH

Hawley K. Linke, PhD

Rosemary E. Riley, PhD, LD

Carol L. Wagner, MD

Mandana Arabi, MD, PhD

Brooke Grindlinger, PhD

Keynote Speaker

Daniel D. Bikle, MD, PhD

Speakers

Ricardo Boland, PhD

Sylvia Christakos, PhD

Luigi Ferrucci, MD, PhD

David G. Gardner, MD

Martin Hewison, PhD

Lily Li

Anastassios G. Pittas, MD

Erica Rutten, PhD

Igor N. Sergeev, PhD, DSc

Carol L. Wagner, MD

Nicholette Zeliadt

Resources

Sylvia Christakos

Martin Hewison

David G. Gardner

Carol L. Wagner

Igor N. Sergeev

Erica Rutten

Lily Li

Anastassios G. Pittas

Ricardo Boland

Luigi Ferrucci

Daniel D. Bikle

Rafael Pérez-Escamilla works to create and implement public health nutrition programs around the world, but realizes that effective programs must take both a global and local view.

Improving Food Security Governance

A Goal to Help All

Developed Countries Not Immune

Academy member Chinua Akukwe answers the “call to duty” as he uses his public health expertise to combat the spread of HIV/AIDS, specifically in Africa.

The neuroscientist and former Academy board chair broke scientific and social ground throughout her long career.

First Female Department Chair

“Science is an adventure; it’s the human search for knowledge and new ideas that can better humankind.”

Funding Reform

Matter of Perspective

Academic and industry researchers, technology developers, and clinicians discuss the progress and the challenges in the field of personalized cancer medicine.

Systemic Problems, Clinical Medicine, and Technology

“We want to know why, for example, not all tumors respond to vascular endothelial growth factor inhibitors. We want to understand resistance.”

**Why did you sign on as an advisor for Contagion?**